Врожденные мышечные дистрофии: классификация и диагностика

Congenital muscular dystrophies (CMD) are a large group of genetically determined muscular diseases, initially defined by an early onset before the age of walking and dystrophic changes on myopathologic analyses. Currently, their definition is less restrictive with, a clinical continuum with limb-girdle muscular dystrophies, and closer histomorphological aspects with congenital myopathies. We distinguish 9 different forms of DMC, classified in 6 different groups depending on the location and/or function of the protein involved, on the control of 26 different genes. Ullrich's disease, UCMD (collagenopathy involving three different genes: COL6A1, COL6A2, COL6A3); secondary dystroglycanopathies (by abnormal glycosylation of alpha-dystroglycan involving 16 different genes); and DMC merosin negative, MDC1A, (merosinopathy secondary to mutations in a unique gene, LAMA2); represent the three most common forms. Rigid spine syndrome type 1, RSMD1 (selenopathy secondary to SEPN1 gene mutation) and L-CMD (laminopathy involving LMNA gene) are also part of the most current forms. Clinical features, plasmatic creatine kinase elevation or not, the presence or absence of clinical signs of central nervous system involvement, allow a first level of diagnostic pathway. According to these elements, muscle and/or cerebral MRI, muscle and/or skin biopsy will be discussed to guide the molecular investigations that will allow accurate diagnosis.Врожденные мышечные дистрофии (ВМД) составляют клинически и генетически чрезвычайно гетерогенную группу мышечных заболеваний. Изначально ВМД рассматривались как группа болезней с дебютом в раннем детском возрасте, до начала самостоятельной ходьбы, и наличием признаков дистрофии при патогистологическом исследовании. Сегодня ВМД подразделяют не столь строго. Так, имеется целый спектр клинических форм, включающий дистрофии поясов с более поздним дебютом игистологической картиной, сближающей их с врожденными миопатиями. Различают 9 форм ВМД, распределенных на 6 групп согласно локализации и/или функции нарушенного белка и соответствующего одному из 26 генов. Чаще всего встречаются следующие формы ВМД: болезнь Ульриха (коллагенопатия, связанная с патологией 3 генов: COL6A1, COL6A2, COL6A3); вторичные дистрогликанопатии (нарушение гликозилирования α-дистрогликана с вовлечением 16 генов) и мерозин-дефицитная ВМД (мерозинопатия, обусловленная мутацией одного гена LAMA2). К классическим формам ВМД также относятся синдром ригидного позвоночника 1-го типа (селенопатия вследствие мутации гена SEPN) и L-ВМД (ламинопатия, вовлекающая ген LMNA). Диагностический поиск определяется выявлением характерной клинической картины, наличием или отсутствием признаков поражения центральной нервной системы, нормальным или умеренно повышенным уровнем креатинфосфокиназы. Выбор молекулярного исследования для уточнения диагноза определяется результатами предварительного лабораторно-инструментального обследования, включающего магнитно-резонансную томографию мышц и/или головного мозга, биопсии мышцы и/или кожи

Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q

Benign familial infantile convulsions (BFIC) are an autosomal-dominant epileptic syndrome characterized by an age of onset within the first year of life. Although they were first reported in families of Italian descent, BFIC have also been described in non-Italian families. We have mapped the BFIC gene to chromosome 19 by linkage analysis in five Italian families with a maximum two-point lod score of 6.36 at D19S114; maximum multipoint lod scores >8 were obtained for the interval D19S250-D19S245. BFIC are therefore the third idiopathic partial epileptic syndrome to be mapped on the human genom

AP4 deficiency: A novel form of neurodegeneration with brain iron accumulation?

OBJECTIVE: To describe the clinico-radiological phenotype of 3 patients harboring a homozygous novel AP4M1 pathogenic mutation. METHODS: The 3 patients from an inbred family who exhibited early-onset developmental delay, tetraparesis, juvenile motor function deterioration, and intellectual deficiency were investigated by magnetic brain imaging using T1-weighted, T2-weighted, T2*-weighted, fluid-attenuated inversion recovery, susceptibility weighted imaging (SWI) sequences. Whole-exome sequencing was performed on the 3 patients. RESULTS: In the 3 patients, brain imaging identified the same pattern of bilateral SWI hyposignal of the globus pallidus, concordant with iron accumulation. A novel homozygous nonsense mutation was identified in AP4M1, segregating with the disease and leading to truncation of half of the adap domain of the protein. CONCLUSIONS: Our results suggest that AP4M1 represents a new candidate gene that should be considered in the neurodegeneration with brain iron accumulation (NBIA) spectrum of disorders and highlight the intersections between hereditary spastic paraplegia and NBIA clinical presentations

Polyradiculonévrite aiguë de l'enfant (étude rétrospective de 42 cas)

MONTPELLIER-BU Médecine (341722104) / SudocMONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les hématomes sous-duraux du nourrisson

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Les vertiges aigus de l'enfant (devenir à long terme)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Linkage of Benign Familial Infantile Convulsions to Chromosome 16p12-q12 Suggests Allelism to the Infantile Convulsions and Choreoathetosis Syndrome

The syndrome of benign familial infantile convulsions (BFIC) is an autosomal dominant epileptic disorder that is characterized by convulsions, with onset at age 3–12 mo and a favorable outcome. BFIC had been linked to chromosome 19q, whereas the infantile convulsions and choreoathetosis (ICCA) syndrome, in which BFIC is associated with paroxysmal dyskinesias, had been linked to chromosome 16p12-q12. BFIC appears to be frequently associated with paroxysmal dyskinesias, because many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 ICCA region. Moreover, one large pedigree with paroxysmal kinesigenic dyskinesias only, has also been linked to the same genomic area. This raised the possibility that families with pure BFIC may be linked to chromosome 16 as well. We identified and studied seven families with BFIC inherited as an autosomal dominant trait. Genotyping was performed with markers at chromosome 19q and 16p12-q12. Although chromosome 19q could be excluded, evidence for linkage in the ICCA region was found, with a maximum two-point LOD score of 3.32 for markers D16S3131 and SPN. This result proves that human chromosome 16p12-q12 is a major genetic locus underlying both BFIC and paroxysmal dyskinesias. The unusual phenotype displayed by one homozygous patient suggests that variability of the ICCA syndrome could be sustained by genetic modifiers

A recessive Na v 1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis

International audienc

Severe phenotypic spectrum of biallelic mutations in PRRT2 gene

International audienceBACKGROUND:Heterozygous dominant mutations of PRRT2 have been associated with various types of paroxysmal neurological manifestations, including benign familial infantile convulsions and paroxysmal kinesigenic dyskinesia. The phenotype associated with biallelic mutations is not well understood as few cases have been reported.METHODS:PRRT2 screening was performed by Sanger sequencing and quantitative multiplex PCR of short fluorescent fragments. A CGH array was used to characterise the size of the deletion at the 16p11.2 locus.RESULTS:Five patients with homozygous or compound heterozygous deleterious PRRT2 gene mutations are described. These patients differ from those with a single mutation by their overall increased severity: (1) the combination of at least three different forms of paroxysmal neurological disorders within the same patient and persistence of paroxysmal attacks; (2) the occurrence of uncommon prolonged episodes of ataxia; and (3) the association of permanent neurological disorders including learning difficulties in four patients and cerebellar atrophy in 2.CONCLUSIONS:Our observations expand the phenotype related to PRRT2 insufficiency, and highlight the complexity of the phenotype associated with biallelic mutations, which represents a severe neurological disease with various paroxysmal disorders and frequent developmental disabilities